Engineered Nano-Micro Pyroptosis Generators: A Magnetic-Metallo-Immunotherapeutic Strategy to Reinforce Transarterial Embolization

作者：Di Wang, Linzhu Zhang, Jihu Nie, Nailin Yang, Shumin Sun, Chunjie Wang, Zifan Pei, Fei Gong, Xingwei Sun, Yong Jin, Liang Cheng · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.5c06039 · 被引用次数：38 · 研究领域：Characterization and Applications of Magnetic Nanoparticles、Extracellular vesicles in disease、Nanoplatforms for cancer theranostics

Gasdermin-mediated pyroptosis represents a promising immunotherapeutic strategy, yet requires precise tumor-specific activation. Magnetic hyperthermia therapy (MHT) has the potential to induce pyroptosis in hepatocellular carcinoma (HCC), while its efficacy is limited by suboptimal heating efficiency and tumor resistance. Herein, we developed an innovative magnetic-metallo-immunotherapeutic platform by engineering nanomicro pyroptosis generators, thereby enhancing transarterial embolization (TAE). Through compositional and structural optimization, Zn–Fe 3 O 4 @Co–Fe 3 O 4 core–shell nanocubes (ZnCo–Fe 3 O 4 CSNCs) with enhanced magnetothermal properties were obtained, which exhibited significantly improved saturation magnetization (Ms) and coercivity (Hc). These nanocubes were further assembled via microfluidic technology into magnetic microspheres (MSs) with tunable sizes, integrating the therapeutic functions of TAE and MHT. Under an alternating magnetic field (AMF), the ZnCo–Fe 3 O 4 MSs demonstrated temperature-dependent ion release and localized hyperthermia while simultaneously inhibiting heat shock protein (HSP) upregulation through metabolic interference. This orchestrated therapeutic cascade effectively triggered pyroptosis in cancer cells, subsequently activating the immune response and thereby enhancing the efficacy of magnetic-metallo-immunotherapy. The strategic combination of this platform with immune checkpoint blockade (ICB) therapy provoked comprehensive syst...